Study of xaluritamig compared to cabazitaxel or androgen receptor therapy for patients with metastatic castration-resistant prostate cancer

Initial enrollment and baseline assessments

After providing informed consent, baseline imaging will be performed. This includes computed tomography (a type of scan that creates detailed pictures of the inside of your body), magnetic resonance imaging (another type of scan that uses magnets and radio waves to create images), or bone scan to confirm the presence of cancer spread.

Blood tests will be conducted to measure testosterone levels (a male hormone) to confirm they are at castrate levels (less than 50 ng/dL or less than 1.7 nmol/L).

Additional blood tests will be performed to check organ function and ensure your body can safely participate in the trial.

Your performance status will be assessed using the Eastern Cooperative Oncology Group scale, which measures how the disease affects your daily living abilities. A score of 0 or 1 is required.

Baseline questionnaires will be completed, including the Brief Pain Inventory - Short Form to assess pain levels, the Functional Assessment of Cancer Therapy - Prostate to evaluate quality of life, and the European Quality of Life - 5 Domain 5 Level Scale to measure overall health status.

Treatment assignment

You will be randomly assigned to one of two treatment groups. Random assignment means that a computer will decide which treatment you receive, similar to flipping a coin.

One group will receive xaluritamig, which is given through a vein (intravenous infusion).

The other group will receive either cabazitaxel (given through a vein) or a second androgen receptor-directed therapy (taken by mouth). The specific treatment will be chosen by your physician based on your medical situation. Androgen receptor-directed therapies may include enzalutamide or abiraterone acetate.

You will continue receiving androgen-deprivation therapy throughout the study to maintain low testosterone levels. This may involve ongoing medication or will have been achieved through surgical removal of the testicles.

Treatment administration

If assigned to receive xaluritamig, the medication will be administered as an intravenous infusion. This means it will be given directly into a vein through a needle or catheter.

If assigned to receive cabazitaxel, it will also be administered as an intravenous infusion.

If assigned to receive a second androgen receptor-directed therapy such as enzalutamide or abiraterone acetate, these medications will be taken orally (by mouth).

Some patients may also receive siltuximab as an intravenous infusion, depending on the specific treatment plan.

Treatment will continue according to the prescribed schedule until disease progression, unacceptable side effects occur, or other reasons require stopping treatment.

Regular monitoring and assessments

Throughout the treatment period, regular imaging scans will be performed to assess how the cancer is responding to treatment. These will be reviewed by independent radiologists who are not involved in your direct care.

Blood samples will be collected periodically to measure prostate-specific antigen (PSA), a protein produced by prostate cells that can indicate disease activity.

If receiving xaluritamig, additional blood samples will be taken to measure drug levels in your blood. These measurements include maximum concentration, time to maximum concentration, minimum concentration, and area under the concentration-time curve, which help determine how the drug moves through your body.

Blood tests will also check for the development of anti-xaluritamig antibodies, which are proteins your immune system might produce in response to the medication.

Regular assessments will monitor for any side effects or adverse events throughout the treatment period.

Quality of life assessments

You will complete the Brief Pain Inventory - Short Form questionnaire regularly to report pain levels, including worst pain, pain intensity, and how pain interferes with daily activities.

The Functional Assessment of Cancer Therapy - Prostate questionnaire will be completed to assess overall quality of life and cancer-related symptoms.

The European Quality of Life - 5 Domain 5 Level Scale will be used to evaluate general health status and includes a visual scale where you rate your overall health.

You will complete selected questions from the Patient-Reported Outcomes version of the Common Terminology Criteria Adverse Events to report symptomatic side effects.

These assessments will track changes from baseline and identify any worsening or improvement in symptoms over time.

Response evaluation

The response to treatment will be evaluated using imaging scans according to modified RECIST version 1.1 criteria, which are standard guidelines for measuring tumor response, combined with Prostate Cancer Working Group 3 criteria specific to prostate cancer.

Objective response will be assessed, which means whether tumors have shrunk or disappeared.

If tumors respond to treatment, the duration of response will be measured, tracking how long the beneficial effect lasts.

Time to response will be calculated, measuring how long it takes from starting treatment until a response is observed.

Disease control will be evaluated, which includes stable disease, partial response, or complete response.

PSA50 response (a decrease of at least 50% in PSA levels) and PSA90 response (a decrease of at least 90% in PSA levels) will be measured.

Monitoring for disease progression

Radiographic progression-free survival will be tracked, which measures the time from starting treatment until the cancer grows or spreads based on imaging scans.

Overall survival will be monitored throughout the study and follow-up period.

The time to first symptomatic skeletal events will be assessed. These are bone-related complications such as fractures, need for radiation to bone, or need for surgery on bone.

Regular imaging will continue to detect any signs of disease progression according to established criteria.

Safety monitoring

Treatment-emergent adverse events will be monitored continuously. These are any medical problems that occur or worsen during treatment.

Serious adverse events and fatal adverse events will be carefully tracked and reported.

If you experience side effects that worsen your pain or quality of life, the time to this worsening will be documented.

For patients with moderate to severe pain at the start of treatment, the time to pain improvement will be measured.

If pain or quality of life worsens and then improves, this pattern will be tracked.

End of treatment

Treatment will end when the cancer progresses, unacceptable side effects occur, you decide to withdraw, or your physician determines it is in your best interest to stop.

Final assessments will be performed at the end of treatment, including imaging scans, blood tests, and quality of life questionnaires.

All ongoing side effects will be documented and monitored until resolution or stabilization.

Follow-up period

After treatment ends, you will enter a follow-up period that will continue until November 2029.

During follow-up, your survival status and subsequent treatments will be tracked.

Long-term outcomes, including overall survival, will continue to be monitored.

Any delayed side effects or long-term effects of treatment will be assessed during this period.